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Researchers developing 3D cell culture models to advance drug discovery

11 July 2024 | Story André Damons | Photo supplied

FARMVOS — From top (left to right): Dr Angélique Lewies (researcher from the Robert WM Frater Cardiovascular Research Centre within the UFS Department of Cardiothoracic Surgery), Zurika Murray (behavioural geneticist from the UFS Department of Genetics), Dr Marieka Gryzenhout (C-rated scientist and Senior Lecturer in the Department of Genetics), and Dr Jaco Wentzel (serves as the pharmaceutical industry partner and consultant for the project at FARMOVS).

In an effort to advance drug discovery and disease research, researchers from the University of the Free State (UFS), the Central University of Technology (CUT), and FARMOVS, a clinical research company associated with the UFS, is developing innovative 3D cell culture models using 3D printed mini bioreactors.

This interdisciplinary project, led by Dr Angélique Lewies, researcher from the Robert WM Frater Cardiovascular Research Centre (Frater Centre) within the UFS Department of Cardiothoracic Surgery, is creating more accurate and human-like models for this purpose, reducing the need for animal testing, and improving the safety and effectiveness of new treatments.

The project was initiated to address the challenges associated with current 3D cell culture techniques, which are often expensive and complex. Recognising the need for a more cost-effective and user-friendly solution, the researchers embarked on this collaboration to develop a novel 3D cell culture system. By making these advanced techniques more accessible, the team aims to enhance the reliability of drug testing and significantly reduce the reliance on animal experiments. This innovative approach not only promises to cut costs but also promotes ethical research practices in the scientific community.

Dr Lewies, whose research specialises in cardio-oncology (relationship between cancer treatment and heart health), particularly in understanding and preventing damage to cardiac cells caused by chemotherapy, leads the cell biology aspects of the project, focusing on the cultivation of 3D cancer spheroid and organoid cultures.

According to her, the project focuses on creating 3D cell cultures, known as spheroids and organoids, that mimic human tissues more closely. These 3D models can improve the reliability of drug testing and reduce the need for animal experiments, aligning with the 3R principles: Reduction, Replacement, and Refinement.

Creating a versatile platform

“Traditional drug discovery and disease studies often rely on flat (2D) cell cultures and animal models. While animal models are essential for understanding disease and testing drug safety, they don't always predict how humans will respond, and their use raises ethical concerns.

“We aim to develop affordable and efficient 3D-printed mini bioreactors for growing these advanced cell cultures. These bioreactors will be designed to fit into existing cell culture labs, making them accessible to researchers. By leveraging the cutting-edge 3D printing technology at CUT's Centre for Rapid Prototyping and Manufacturing (CRPM), the team hopes to create a versatile platform for various research applications,” says Dr Lewies.

She is joined in this project by UFS colleagues; Zurika Murray, a behavioural geneticist, and her colleague from the Department of Genetics, Dr Marieka Gryzenhout, a C-rated scientist and Senior Lecturer. Dr Jaco Wentzel from FARMOVS. is also involved in the project. Dr Wentzel serves as the pharmaceutical industry partner and consultant for the project. With experience in cellular biology and pharmaceuticals, he ensures that the new 3D cell culture models meet industry standards and can be effectively used in drug development. Dr Wentzel’s role is crucial in bridging the gap between academic research and practical application in the pharmaceutical industry.

Goals

According to Dr Lewies, this project aims to create more accurate and ethical models for drug testing and improving the development of new treatments. By combining expertise from engineering, biology, and mycology, the team is set to revolutionise how diseases are studied, and medicines developed. Funded by the CUT and UFS Joint Research Programme, this initiative promises to foster innovation and lead to new research collaborations.

“Cardiac cell damage, known as cardiotoxicity, can lead to serious cardiovascular diseases and is a major reason why some drugs are removed from the market. By developing 3D cancer spheroids and cardiac organoids (mini heart models), my team aims to find ways to prevent this cardiotoxicity while enhancing the effectiveness of chemotherapy drugs.

“Additionally, they are exploring the cardiotoxic effects of natural products, such as medicinal plants and mushrooms, which show potential for both anticancer and cardio-protective properties,” says Dr Lewies.

Experts

Murray is interested in how the psychedelic compounds psilocybin and psilocin affect the brain with her research focusing on the epigenome of genes within the serotonin pathway, which could explain the therapeutic potential of these compounds. “As part of this project, Murray will work with the Frater Centre to develop neuronal organoids (mini brain models) using the 3D mini-bioreactor platform.

“This will allow her to investigate the effects of psilocybin and psilocin on brain function, which have shown promise in treating mental health disorders like depression and anxiety, aiming to understand how these substances might help treat mental health issues,” says Dr Lewies.

Dr Gryzenhout brings her expertise in mycology and is responsible for cultivating medicinal mushrooms used in the project. Dr Gryzenhout's research focuses on the genetic characterisation of medicinal mushrooms and evaluating their therapeutic potential. These mushrooms produce a variety of bioactive compounds with therapeutic benefits, including anticancer activities, heart protection, and immune system support.

Her team is also approved by the South African Health Products Regulatory Authority (SAHPRA) to research the controlled psychedelic compounds psilocybin and psilocin.

Drug Discovery Goals

The project’s long-term focus is on potentially discovering new drugs to prevent and treat heart and brain diseases. Specifically, the team is working on developing therapies for cardio-oncology and neurological applications. In the realm of cardio-oncology, the goal is to find treatments that prevent cardiac cell damage and downstream cardiovascular diseases caused by cancer therapies, while still effectively targeting cancer cells. For neurological applications, the researchers are exploring the potential of drugs derived from medicinal mushrooms, including those with psychedelic properties, to treat conditions like depression, anxiety, and other mental health disorders.

News Archive

An education system based on hope is what South Africa needs – Dr Beryl Botman

2016-05-26

Description: Hope revised Tags: Hope revised

Dr Beryl Botman, a postdoctoral research
fellow at the IRSJ, with Dr Willy Nel research associate
at the IRSJ and lecturer at the UFS
Faculty of Education.

HOPE is tangible and concrete construct that should be rooted in the learning and training of teachers,” said Dr Beryl Botman, a postdoctoral research fellow at the Institute for Reconciliation and Social Justice (IRSJ).

She presented her research paper Educators, praxis, and hope: A philosophical analysis of post-apartheid teacher education policy, based on the theoretical ideologies of Paulo Freire’s Pedagogy of the Oppressed. She explores ways in which oppression has been justified, and how it has been overcome through a mutual process between the oppressor and the oppressed, drawing on Paolo Freire’s theories and practices. The presentation was held at the University of the Free State’s (UFS) Faculty of Education, on the Bloemfontein campus on 13 May 2016.

From oppression to hope
Hope should be an educational construct for teacher education in South Africa. Dr Botman asserts that epistemology and ontology should be inseparable, as they are pivotal to an education system that is transformational.

The recent country-wide student protests and demonstrations are an indicant that education institutions need to seek understanding of mechanisms that fuel social conflict. Dr Botman claims that vast social inequalities make the process of democratisation difficult thus hindering transformation. She states that a critical consciousness is important for all South Africans, but more so for educators; it can be used as a tool to understanding the mechanisms of social conflict.

“Self-reflection and self-critique is vital for educators, we need to understand that we do not have all the answers because we ever-evolving beings, working on understanding ourselves and the people around us,” said Dr Botman.

The notion of hope
“I am a farmer. I have no hope for a future that is different from today. This quotation comes from Paulo Freire’s work," said Dr Botman. She said that the South African context and environment is similar. She said that people cannot live for today; one should live for tomorrow if hope is to manifest itself.

South African education environment needs to adopt a progressive consciousness that is future orientated, “You need to be hopeful, if you are radical. You need to be able to envision a new society and a new world,” said Dr Botman.

“You cannot only denounce the present, you need to also announce your hopes for a new society. South Africa needs education systems built on understanding. Although change is difficult, it is necessary for transformation,” Dr Botman added.

What makes hope educational?
“Hope is a vision for a tomorrow that is different, and vital for a transformative education system. To get out of a state of despair, people need to educate their hope. Lately, the issue of white privilege has been brought to the fore. You need to educate your hope, so that you understand the reality of others but, more importantly, of yourself,” said Dr Botman.

Dr Botma added that teacher education needs to adopt a Freirean pedagogy with a strong philosophy based on hope. The agency of teachers can either be hopeful or without hope. It is vital that education promotes hope.

“Teachers need to rely on their existential experience, the experiences of others, and the experiences of the children or students they teach. An understanding of all these experience reinforces the idea that people are life-long learners, always learning and adapting to society’s needs,” said Dr Botman.

Teachers as agents of hope
Dr Botman stated that current South African education policy is directed towards transformation but it does not stipulate means to achieve this objective. Further, she argues that educators need to put greater emphasis on self-knowledge, self-reflection, and self-education. Connecting with teachers, parents, students and the community engages with their self-knowledge and reflection.

Reorientation of teacher education
Dr Botman concluded by mentioning that rethinking ontological and epistemological aspects of education is important, and should be a pivotal point of teacher education. A renewed vision of hope-orientated philosophy and pedagogy needs to be adopted by the education institutions. A praxis, which is an informed action, when a balance between theory and practice is achieved. There is a need for an inclusive exploration of education philosophies and education systems not only European and Western but also African and Eastern as well.

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